The investigators? goal is to become a clinician-scientist focused on African-American health and hypertension research using the tools of population genetics, molecular biology, and blood pressure (BP) physiology. To realize his goal, he designed a program of coursework, structured mentoring by senior investigators, and innovative research. With regards to continuing coursework, he was awarded a Master?s degree in health science in epidemiology this year and will continue advanced coursework at JHU and the JH Bloomburg School of Public Health in the fields of population genetics and molecular biology. In addition, he will continue to meet weekly with his sponsor and to meet regularly with his Advisory Committee of senior investigators. With the support of his sponsor and co-investigators, he proposes a case-control study of 300 African-American persons with severe hypertension admitted to the JH Hospital, 200 normotensive siblings, and 300 community-dwelling controls with a negative family history of hypertension and a low normal BP measured at two points in time four years apart. The prevalence of gene variants and candidate exposures will be compared between the cases and two sets of controls. In addition, the investigators will investigate gene-gene and gene-environment interactions. Through a newly formed collaboration with Dr. Aravinda Chakravarti and the McKusick-Nathans Institute of Genetic Medicine (IGM), the study will benefit from advanced genotyping technology that will allow the identification of hundreds of alleles at hundreds of loci. This study is distinguished by the recruitment of individuals representing extremes of the BP distribution, the recruitment of sibling controls, the characterization of proximal phenotypes, measurement of environmental exposures, and the use of advanced genotyping technology. In addition, the inclusion of inner city African-Americans will fill a major gap in the understanding of BP regulation. This ambitious study is feasible because of support from the GCRC, the infrastructure of the Core Laboratory of the IGM, the investigator?s 10-year relationship with the community, his demonstrated recruitment success, and the commitment of his mentors and sponsor. This research will build a foundation for a successful career as an independent investigator.